Miguel Lopez Cuina

Physiopathologie et traitement de l'atrophie multisystématisée

novembre 2019 Directeur(s) de thèse : Wassilios Meissner Résumé de thèse

This PhD work focused, on the one hand, on translational approaches aiming to reduce the accumulation of α-synuclein in an animal model of MSA, and on the other hand, on a pathological analysis of a rare subtype of the disease.

Throughout the three years of work, we have assessed different therapeutic candidates in an animal model of MSA. Rapamycin, a drug known to enhance autophagy and protein clearance, showed only a partial neuroprotective effect against neural loss in our model. Nilotinib, a drug that had shown neuroprotective properties in a Parkinson’s disease animal model, failed to modify the disease course in our study. Finally, we evaluated the combinations of two drugs that have already proven to reduce a-synuclein aggregation and protect neurons from degeneration, to assess whether they have synergistic properties.

Keywords : Synuclein, Multiple system atrophy, glial cytoplasmic inclusions, post-mortem human brain study, rodent, translational approach, c- terminal truncation, phosphorylation, autophagy, protein aggregation.